A supplement to Grant No. R01-DA-00125 is being requested to enable completion of work on the immunologic effects of morphine during a 6- month extension of the original grant period. Work to be completed includes studies now in progress on animals ( rabbits and monkeys) given long-term morphine treatment, and tests on stored (frozen) sera remaining from previous experiments on a number of species (rabbits, rats, guinea pigs, cats and monkeys). Animal studies will include measurement of the effects in rabbits of immunosuppressive treatment (cyclophosphamide), heroin pellet administration, and animal sex on the development of the serum morphine-binding response. Cynamolgus monkeys are now being given additional morphine pellet treatment to obtain large quantities of serum for fractionation and analysis. Further lymphocyte- activation testing is scheduled for both rabbits and monkeys to measure the effects of morphine treatment on lymphoxyte responses to phytohemagglutinin and to morphine-carrier antigens. Studies on stored sera include (1) immunologic tests on sera from rats immunized against a morphine-carrier conjugate (to measure effects of morphine treatment on immunologic responsiveness to the conjugate), (2) retesting of sera from various morphine-treated species to measure morphine-binding characteristics, (3) fractionation of selected sera by preparative polyacrylamide gel electrophoresis and Sephadex gel chromatography methods to identify more definitively the morphine-binding serum component, (4) further immunologic testing of the morphine-binding sera and serum fractions, and (5) quantitative measurement of binding capacity and binding specificity of selected morphine-binding sera from a number of test species.